organ microenvironment
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2021 ◽  
Vol 17 (7) ◽  
pp. e1009193
Author(s):  
Vlada S. Rozova ◽  
Ayad G. Anwer ◽  
Anna E. Guller ◽  
Hamidreza Aboulkheyr Es ◽  
Zahra Khabir ◽  
...  

Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET), are believed to play key roles in facilitating the metastatic cascade. Metastatic lesions often exhibit a similar epithelial-like state to that of the primary tumour, in particular, by forming carcinoma cell clusters via E-cadherin-mediated junctional complexes. However, the factors enabling mesenchymal-like micrometastatic cells to resume growth and reacquire an epithelial phenotype in the target organ microenvironment remain elusive. In this study, we developed a workflow using image-based cell profiling and machine learning to examine morphological, contextual and molecular states of individual breast carcinoma cells (MDA-MB-231). MDA-MB-231 heterogeneous response to the host organ microenvironment was modelled by substrates with controllable stiffness varying from 0.2kPa (soft tissues) to 64kPa (bone tissues). We identified 3 distinct morphological cell types (morphs) varying from compact round-shaped to flattened irregular-shaped cells with lamellipodia, predominantly populating 2-kPa and >16kPa substrates, respectively. These observations were accompanied by significant changes in E-cadherin and vimentin expression. Furthermore, we demonstrate that the bone-mimicking substrate (64kPa) induced multicellular cluster formation accompanied by E-cadherin cell surface localisation. MDA-MB-231 cells responded to different substrate stiffness by morphological adaptation, changes in proliferation rate and cytoskeleton markers, and cluster formation on bone-mimicking substrate. Our results suggest that the stiffest microenvironment can induce MET.


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Mohammad A. Alzubi ◽  
Tia H. Turner ◽  
Amy L. Olex ◽  
Sahib S. Sohal ◽  
Nicholas P. Tobin ◽  
...  

Author(s):  
Sun-Jin Kim ◽  
Ho Jeong Lee ◽  
Hyunkyung Yu ◽  
Sung II Choi ◽  
John Weinstein ◽  
...  

2012 ◽  
Vol 5 (1) ◽  
pp. 133-137 ◽  
Author(s):  
GUOCAI LI ◽  
LUNXIU QIN ◽  
QINGHAI YE ◽  
QIONGZHU DONG ◽  
NING REN ◽  
...  

2010 ◽  
Vol 101 (9) ◽  
pp. 1965-1969
Author(s):  
Daisuke Sugiura ◽  
Kaori Denda-Nagai ◽  
Kazuyoshi Takeda ◽  
Tatsuro Irimura

2007 ◽  
Vol 28 (3) ◽  
pp. 297-321 ◽  
Author(s):  
Robert R. Langley ◽  
Isaiah J. Fidler

2007 ◽  
Vol 101 (4) ◽  
pp. 927-936 ◽  
Author(s):  
Isaiah J. Fidler ◽  
Sun-Jin Kim ◽  
Robert R. Langley

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